A new Oregon Health & Science University and Portland
Veterans Affairs Medical Center study suggests that early-stage
Parkinson's disease patients who lower their calorie intake
may boost levels of an essential brain chemical lost from
the neurodegenerative disorder.

The study by Charles Meshul, Ph.D., associate professor
of behavioral neuroscience in the OHSU School of Medicine
and the VAMC's Neurocytology Lab, shows that dietary restriction
reverses a Parkinson's-induced drop in glutamate, a brain
neurotransmitter important for motor control, function
and learning, in a mouse model for the disease's early
stages.

The results, presented at the Society for Neuroscience's
35th annual meeting in Washington, D.C., are the first
to show that a restricted diet can disable neurochemical
changes in the brain occurring in early-stage Parkinson's
even after those changes are observed.

"In the early stages of the disease, we see certain
markers in the brain that are changing that may be indicative
that dietary restriction is helpful," Meshul said.

Parkinson's disease is a progressive, degenerative disorder
affecting a region of the brain called the substantia
nigra where movement is controlled. Symptoms such as tremor
or shaking, muscular stiffness or rigidity, slowness of
movement and difficulty with balance appear when about
80 percent of cells in the body that produce the neurochemical
dopamine die or become impaired.

Incidence increases with age, and the disease is uncommon
in people younger than 40. According to the OHSU Parkinson
Center of Oregon, the disease affects both men and women
across all ethnic lines and occurs in about two of every
100 people older than 55. About 1.5 million Americans
suffer from the disease.

Meshul's lab compared two groups of mice with 60 percent
to 75 percent loss of dopamine in the brain, representing
early-stage Parkinson's: One had access to food every
day while the other had access every other day, and both
were fed over a 21-day period. The mice that ate less
often lost 10 percent to 15 percent of their body weight
compared to their counterparts.

"Dietary restriction appears to be normalizing the levels
of glutamate," Meshul said. "The fact that we're getting
the levels of glutamate back to, essentially, control
levels may indicate there are certain synapse changes
going on in the brain to counteract the effects of Parkinson's.
In fact, what this may indicate is a reversal of locomotor
deficits associated with the disease."

In addition to the rise in glutamate, Meshul's group,
using a dopamine-synthesizing enzyme called tyrosine hydroxylase
as a marker for dopamine nerve terminals, found that dietary
restriction caused a drop in the number of dopamine terminals
in the mouse model for early-stage Parkinson's.

"As it turns out, dietary restriction, in and of itself,
had an effect. It actually caused a small but significant
decrease in the numbers of these dopamine terminals. So
in other words, dietary restriction really is doing something
to the brain," Meshul said. "It could very well be that
what dietary restriction is doing is trying to protect
the system somehow. And one of the reasons dietary restriction
is protective may be that it's reducing the activity of
particular synapses. That's actually what the data indicates."

Matching the upturn in glutamate levels with positive
behavioral changes is difficult at this point in the research,
Meshul said. "One of the unfortunate problems with this
model is it's tough to do any behavioral measures. We
see a reversal of the effect of glutamate in the brain
due to the dietary restriction, but what does that actually
mean in terms of the behavior of the animal? Unfortunately,
we don't know. We didn't measure that."

But a similar primate study at the University of Southern
California that Meshul is associated with is testing the
hypothesis that glutamate does have an effect on behavior.
"It turns out that, in time, these animals recover behaviorally
from all of the motor deficits that are associated with
(early-stage Parkinson's)," he said. "Our hypothesis is
there may be changes in glutamate that account for these
behavioral changes."

Dietary restriction's beneficial effect on neurological
function has been studied in primates by scientists at
the National Institutes of Health for 30 years, Meshul
said. Researchers found that animals whose calorie intake
was lowered by 20 percent aged better, suffered from fewer
immunological disorders, displayed healthier hair and
skin tone, and "looked significantly better than a counterpart
that hasn't had a restricted diet."

"They live longer," Meshul said. "It's been known for
many, many years that dietary restriction is good."

Scientists already have shown dietary restriction initiated
before the onset of early Parkinson's can protect against
neurochemical changes in the brain caused by the disease.
In 1999, researchers found that mice on restricted diets
for three months prior to an early Parkinson's diagnosis
lost fewer dopamine-synthesizing neurons.

"There's not as much loss of dopamine if you restrict
their diets ahead of time," Meshul noted.

Meshul's lab is finding that dietary restriction isn't
the only way to boost neurological function in Parkinson's
disease. Early results of another study the group is conducting
have shown that rats with 90 percent loss of dopamine
in the brain - or full-blown Parkinson's disease - under
a four-week exercise regimen can run twice as long as
parkinsonian rats that didn't exercise.

"We're trying to make the correlation that exercise
definitely helps in terms of the parkinsonian animal and,
in fact, in human studies it's been shown that any sort
of exercise helps patients," Meshul said.